Summary

Currently, for further improved survival outcome, new cytotoxic compounds such as irinotecan
and docetaxel have been combined with 5-FU/cisplatin. However, triplet regimen often
burdened with higher toxicity and serious neutropenic infection. Therefore, future trials in
neoadjuvant and adjuvant settings need to incorporate new molecular agents which improve
efficacy, but less toxicity.

Additional Information

Though a significant decrease in its incidence over the last 70 years, gastric cancer
remains a significant health problem worldwide. Despite the R0 resection and adjuvant
chemotherapy, the prognosis for patients with locally advanced GC remains poor, with 5-year
survival rate below 60%. Therefore, active strategy to improve survival outcome is ongoing
in gastric cancer. Due to the nature of gastric surgery, postsurgical recovery can be
avoided by the administration of systemic therapy and/or radiation prior to the surgical
procedure. Furthermore, preoperative therapy has the theoretical advantage of treating an
untouched tumor (lack of treatment-induced resistance), with intact vascularization and
without fibrotic remodeling of the tumor bed due to surgical trauma. These considerations
addressed clinical trials incorporating neoadjuvant treatment for gastric cancer.
Preoperative chemotherapy proved superiority to surgery alone in esophagogastric junction
cancer Regarding the pattern of failure, locoregional recurrence after surgical resection
has been reported 20-50% of cases. To improve local control and survival outcome,
chemoradiotherapy in the neoadjuvant or preoperative setting has been widely applied. In
recently published meta-analysis, preoperative chemoradiotherapy combined with surgery
significantly reduced the 5-year death rate compared to surgery alone (OR 0.57, P=0.001).
Ajani et al reported phase II preoperative chemoradiotherapy (5-fluorouracil/cisplatin and
45 Gy radiotherapy) for localized gastric cancer. Among the 34 stage II/III gastric cancer
patients, 30% had pathologic complete response and 24% had pathologic partial response (<10%
residual carcinoma). Lowy et al also demonstrated 11% and 63% of complete, partial
pathologic responses and preoperative chemoradiotherapy was safe and well tolerated. Based
on those rationale, 28 clinical trials with neoadjuvant chemotherapy is ongoing for gastric
cancer (clinicaltrial.gov) and the investigators' center is also conducting neoadjuvant
chemoradiotherapy trial for localized gastric cancer (NCT01269255).Currently, for further
improved survival outcome, new cytotoxic compounds such as irinotecan and docetaxel have
been combined with 5-FU/cisplatin. However, triplet regimen often burdened with higher
toxicity and serious neutropenic infection. Therefore, future trials in neoadjuvant and
adjuvant settings need to incorporate new molecular agents which improve efficacy, but less
toxicity.